Procedural modifications proposed for the screening of substances extracted from pharmaceutical packaging systems and medical devices with the goal of improving inter-laboratory consistency of the data generated

Abstract

Substances that migrate (leachables) into a pharmaceutical product from the materials that comprise its manufacturing, packaging, and/or delivery system(s) have the potential to negatively impact its safety and/or quality. Mitigating the impact of this interaction typically includes the screening of substances that can be extracted (extractables) from these materials using appropriate solvents and exposure conditions. Despite the importance of such extractable screening studies in assuring product quality and patient safety, it has become apparent that inconsistencies in their execution between laboratories have resulted in the potential for differences in the qualitative and/or quantitative aspects of the extractable profiles obtained. Since this issue was discovered primarily through anecdotal accounts, a working group within ELSIE conducted two industry surveys that inquired into impactful variables of extractable screening study design and execution. After completion of these surveys, it was concluded that there were numerous variables where labs were not well aligned, which may be impacting the consistency of the data generated to some extent. To that end, this commentary summarizes recommendations proposed by the ELSIE working group to address the discrepancies in extractable study design and ultimately produce more consistent and reliable extractable profiles between laboratories.

Keywords: Extractable; Leachable; Screening study; Surrogate Standard; Uncertainty factor.